US2020261365A1PendingUtilityA1

Process for preparing pharmaceutical compositions

47
Assignee: MERCK SHARP & DOHMEPriority: Dec 16, 2015Filed: Dec 13, 2016Published: Aug 20, 2020
Est. expiryDec 16, 2035(~9.4 yrs left)· nominal 20-yr term from priority
Inventors:Luke Ryan SchenckDavid J. LambertoJoseph L. Kukura, IiFrancisco J. GuzmanAaron S. CoteAthanas Koynov
A61K 9/145A61K 9/5161A61K 9/5146A61K 9/5123A61K 9/5138A61K 9/146A61K 9/10
47
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Claims

Abstract

A process for preparing and isolating pharmaceutical active ingredient particles having a particle size of between about 0.1 and 30 microns, wherein a slurry comprising the active ingredient and one or more pharmaceutically acceptable excipients is fed into a thin film evaporator under suitable conditions for less than 10 minutes sufficient to generate solid matrix particles comprising active ingredient and one or more excipients, wherein the particles have less than 5% residual solvent.

Claims

exact text as granted — not AI-modified
What is claimed is: 
     
         1 . A process for preparing and isolating pharmaceutical active ingredient particles having a particle size of between about 0.1 and 30 microns, wherein a dried solids-containing slurry comprising the active ingredient and one or more pharmaceutically acceptable excipients is fed into a thin film evaporator under shear, temperature and pressure conditions to provide turbulent mixing for less than 10 minutes and sufficient to generate solid matrix particles comprising the active ingredient and the one or more excipients, wherein the particles have less than 5% residual solvent. 
     
     
         2 . A process of  claim 1  for preparing and isolating pharmaceutical active ingredient particles having a particle size of between about 0.1 and 30 microns, wherein the slurry comprising the active ingredient, a steric stability polymer, an electrostatic stability surfactant, and a redispersibility excipient, is fed into the thin film evaporator under shear, temperature and pressure conditions to provide turbulent mixing for less than 10 minutes and sufficient to generate solid matrix particles comprising the active ingredient and the one or more excipients, wherein the particles have less than 5% residual solvent. 
     
     
         3 . A process of  claim 2  for preparing and isolating pharmaceutical active ingredient particles having a particle size of between about 0.1 and 30 microns, wherein the slurry comprising the active ingredient and one or more pharmaceutically acceptable excipients is fed into the thin film evaporator under shear, temperature and pressure conditions to provide turbulent mixing for less than 5 minutes and sufficient to generate solid matrix particles comprising the active ingredient and the one or more excipients, wherein the particles have less than 0.5% residual solvent. 
     
     
         4 . A process of  claim 3  wherein the particles have a particle size of between 0.1 and 5 microns. 
     
     
         5 . A process of  claim 4  wherein the particles have a particle size of between 0.1 and 0.25 microns. 
     
     
         6 . A process of  claim 1  wherein the particles are crystalline. 
     
     
         7 . A process of  claim 1  wherein the particles are amorphous. 
     
     
         8 . A process of  claim 2  wherein the steric stability polymer is a cellulosic polymer, a methacrylate, a vinyl polymer, a copolymer, or polyethylene glycol. 
     
     
         9 . A process of  claim 7  wherein the steric stability polymer is ethyl cellulose, methyl cellulose, hydroxyl propyl cellulose, hydroxylpropyl methyl cellulose, hydroxypropyl methyl cellulose acetate succinate, hydroxylpropyl methyl cellulose phthalate), Poly(butyl methacrylate-co-(2-dimethylaminoethyl), Poly(methacylic acid-co-ethyl acrylate), Poly(methacylic acid-co-methyl acrylate), 1-ethenylpyrrolidin-2-one, copovidone, soluplus, polyethylene oxide (PEO), polyoxyethylene (POE)), or poly(acrylic acid). 
     
     
         10 . A process of  claim 2  wherein the electrostatic stability polymer is Polyoxyethylene (20) sorbitan monooleate, poloxamer, Octadecanoic acid [2-[(2R,3S,4R)-3,4-dihydroxy-2-tetrahydrofuranyl]-2-hydroxyethyl] ester, Sodium 1,4-bis(2-ethylhexoxy)-1,4-dioxobutane-2-sulfonate, D-α-Tocopherol polyethylene glycol succinate, Sodium Lauryl Sulfate, or Lecithin. 
     
     
         11 . A process of  claim 2  wherein the redispersibility excipient is a salt, sugar, sugar alcohol, or polysacharride. 
     
     
         12 . A process of  claim 2  wherein the redispersibility excipient is a cellulosic polymer, a methacrylate, a vinyl polymer, a copolymer, polyethylene glycol, a monosaccharide, a disaccharide, an amino acid or a sugar alcohols. 
     
     
         13 . A process of  claim 12  wherein the redispersibility excipient is ethyl cellulose, methyl cellulose, hydroxyl propyl cellulose, hydroxylpropyl methyl cellulose, hydroxypropyl methyl cellulose acetate succinate, hydroxylpropyl methyl cellulose phthalate), Poly(butyl methacrylate-co-(2-dimethylaminoethyl), Poly(methacylic acid-co-ethyl acrylate), Poly(methacylic acid-co-methyl acrylate), 1-ethenylpyrrolidin-2-one, copovidone, soluplus, polyethylene oxide (PEO), polyoxyethylene (POE)), or poly(acrylic acid). 
     
     
         14 . A process of  claim 12  wherein the the monosaccharide is glucose, fructose, or galactose. 
     
     
         15 . A process of  claim 12  wherein the disaccharide is lactose, maltose, sucrose, cellobiose, or trehalose. 
     
     
         16 . A process of  claim 15  wherein the disaccharide is lactose or trehalose. 
     
     
         17 . A process of  claim 12  wherein the sugar alcohol is mannitol, xylitol, sorbitol, glycerol. 
     
     
         18 . A process of  claim 17  wherein the sugar alcohol is mannitol. 
     
     
         19 . A process of  claim 11  wherein the polysaccharide is raffinose, chitosan, or amylose. 
     
     
         20 . A process of  claim 1  wherein the shear, temperature and pressure conditions to provide turbulent mixing comprise shear rates exceeding 4,000 s −1 , temperature between about 40° C. and 180° C., and vacuum. 
     
     
         21 . A process of  claim 1  wherein the shear, temperature and pressure conditions to provide turbulent mixing comprise shear rates exceeding 4,000 s −1 , temperature between about 40° C. and 180° C., vacuum less that 100 mbar pressure, and Reynolds Numbers above 200,000. 
     
     
         22 . A process of  claim 1  wherein the amount of active ingredient in the slurry dried solids is between about 20-80 wt/wt %. 
     
     
         23 . A process of  claim 22  wherein the amount of active ingredient in the slurry dried solids is between about 35-65 wt/wt %.

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